Expression of kallikrein 7 diminishes pancreatic cancer cell adhesion to vitronectin and enhances urokinase-type plasminogen activator receptor shedding.
OBJECTIVE
To examine the effects of kallikrein 7 (KLK7) expression in pancreatic cancer cells on cell adhesion to extracellular matrix proteins.


METHODS
Kallikrein 7 was overexpressed in the pancreatic cancer cell line BxPC-3, and in vitro cell adhesion assays were performed to determine alterations in cell adhesion to collagen I, fibronectin, and vitronectin compared with vector-transfected cells. Changes in cell surface expression of alphavbeta3 integrin were examined by flow cytometry, and the release of soluble urokinase-type plasminogen activator receptor (uPAR) was monitored by Western blot analysis.


RESULTS
The expression of KLK7 in BxPC-3 cells led to reduced adhesion to vitronectin but not collagen I or fibronectin. Loss of cell adhesion to vitronectin was not caused by changes in the level of alphavbeta3 integrin cell surface expression; however, a significant increase in the amount of uPAR shed was observed in KLK7-expressing cells compared with vector-transfected control cells.


CONCLUSIONS
The aberrant expression of KLK7 in pancreatic cancer cells leads to a reduction in cell adhesion to vitronectin that may result from the cleavage of uPAR from the cell surface. Kallikrein 7 expression, therefore, may play an important role in the dissemination of tumor cells through the production of soluble uPAR in pancreatic cancer and perhaps other human malignancies.
Ramani
Vishnu C
VC
Department of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Haun
Randy S
RS
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D014162:Transfection; D019096:Vitronectin / Q000378:metabolism*
D024042:Collagen Type I; D017077:Culture Media, Conditioned; D005353:Fibronectins; D039302:Integrin alphaVbeta3; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin; C082472:KLK7 protein, human; D007610:Kallikreins